The yellow fever mosquito, Aedes aegypti, is a well known vector of yellow fever (YF) and dengue fever (DEN) flaviviruses. Subspecies and populations of Ae. aegypti vary widely in their ability to transmit flaviviruses. Studies have shown that a midgut barrier to infection exists in the West African subspecies Ae. aegypti formosus. In the other subspecies, Ae aegypti aegypti, we demonstate that viral replication is regulated by genes that control disseminated infection rate. In both subspecies, levels of virus infection vary quantitatively among individuals and are subject to random environmental effects. Recent molecular and statistical advances enable geneticists to map loci affecting the expression of quantitative traits. These have been termed quantitative trait loci (QTLs). The first goal of this project is to map QTLs that control vector competence for DEN virus in Ae aegypti. The genetic markers arising from this project will be tested as biomarkers of DEN susceptibility in populations of Ae aegypti in dengue endemic areas in Mexico. This is a specific aim of another proposal being submitted by Dr. Barry Beaty in response to this PA. The second goal of the proposed work is to use marker-assisted selection (MAS) to generate strains of Ae aegypti that carry the midgut barrier genes in combination with genes that regulate the disseminated infection rate. These strains may be completely refractory to DEN virus and will provide an exceptional opportunity to elucidate the genetic mechanisms underlying DEN transmission. These strains may also have the potential for release into endemic areas of DEN virus transmission. Another specific aim of the Beaty proposal is to identify genetically isolated populations in DEN endemic regions of Mexico.